From the group of earthy alkalies we can exclude the first and last member: beryllium, a rare element in the earth which has no physiologic and so far as we know no pharmacologic significance. Radium indeed belongs chemically to this group, but its actions are so dominated by the decomposing radiations that it seems more suitable to consider it later in connection with the other radio- active element, uranium.
There remain the important physiologic elements, magnesium and calcium, which appear with many similarities and many opposites in the organism and then strontium and barium, closely related to calcium but foreign to the body. Common to all is their appearance as divalent cations. They are not so movable and exchangeable as the alkali cations. The relation of the earthy alkalies to water is likewise different and their salts are poorly soluble. Likewise they are in opposition to the univalent cations in their influences upon colloids. Yet magnesium stands in an intermediate position, and it also has a special position chemically opposite to the heavier elements of the group.
In the actions on the organism the group relationships of these four elements comes distinctly into appearance.
Magnesium has a circulation in the earth similar to that of calcium between the lithosphere and hydrosphere: it is found in the upper earth surface in great amounts (about 2.5 per cent; calcium about 3.5 per cent) chiefly as the carbonate, alone as magnesite and together with calcium carbonate, as dolomite. As the chloride and sulphate it is associated with potassium salts. Even in this natural appearance it comes now with potassium and now with calcium salts, so that the intermediate position of magnesium between the alkalies and earthy alkalies holds even in relation to the organism.
Magnesium is obviously present in every living cell, indeed in the muscle and nervous tissue the strongest; in the cerebrospinal fluid the magnesium content is higher than in the serum. These are the first suggestions of the very dark role in general of magnesium in the animal organism.
Magnesium metabolism proceeds very slowly. In the serum with its content of 2-4 mg. per cent it is present essentially in smaller amounts than calcium. Just as with calcium it exists there only in part as a free cation, and in other parts bound as a complex anion. One might conceive of this as the first reserve. In any case organic compounds are present in the cells. In the bones the affinity for magnesium is much less than that for calcium.
The physiologic significance of magnesium is best known in the green plants. Here Willstaetter has discovered it in an organic form in chlorophyl- similar to the iron in hemoglobin. One presumes that in the assimilation of carbon dioxide, also a synthetic reduction process, it plays a role similar to that of iron in hemoglobin in the oxidation of carbon compounds. Also in organic chemistry magnesium is often used in synthetic reactions as an intermediator for the introduction of a new radicle. Grignard has shown a catalytic promotion of organic synthesis with organic magnesium compounds. in physiologic animal investigation no great weight is placed upon the presence of magnesium, because Ringer’s solution does not contain magnesium, while on the other hand Tyrode’s solution contains half as much MgCl2 as CaCl2. Probably the greater significance comes to magnesium in the interior of the cell.
ION ACTION ON COLLOIDS AND CELLS
In the influence on colloids magnesium takes a mid position between the alkalies and the earthy alkalies. In its swelling capacity, for example, it stands nearer the alkalies, also in protein salting out and flocculation. The precipitation of hydrophile colloids, perhaps albumin, is reversible through magnesium salts, as with the alkali salts and in concentrations, in which calcium, strontium and barium salts cause irreversible precipitates. For many colloidal effects, as the precipitation of suspension colloids, the positive double valence of magnesium is decisive and in this respect magnesium agrees with the other earthy alkalies as calcium, strontium and barium, and like the other earthy alkalies as an antagonist to sodium and potassium. But outside of the antagonism between the uni- and divalent cations as it appears in living colloids there is also an opposition in the action of magnesium and calcium in the living cell wall as the latter is antagonist of not only magnesium but also the alkalies, which in many cases cause precipitation through swelling. On muscle a swelling action of magnesium has been demonstrated in contradistinction to the de-swelling through calcium. For placing magnesium in equilibrium relatively more calcium is necessary than for sodium and potassium. In an antagonism which manifests itself in the removal of a one-sided damaging influence, the concentration relations are always important.
That the actions of two elements which follow one another in a related group are not additive but subtractive and appear in the end-effects as opposites is something very common as we have already seen in sodium and potassium, and which also occurs with chloride and bromine. This is probably connected with an opposing property of penetration so that closely related ions collect on the site of action, the surface of the colloidal particles. Increased introduction of magnesium provokes an increased excretion of calcium into the urine; thereby calcium goes out of its tissue compounds into ionic form. By increase of the magnesium content in the serum, the binding. capacity of the cartilage for calcium is impaired.
An antagonism between magnesium and calcium can be demonstrated on the frog heart. Addition of magnesium to the nutrient fluid slows the heart beat, lengthens diastole and ends finally in standstill in diastole (this action is also shown from intravenous injections on the entire animal) while reversely calcium increase accelerates the cardiac action, lengthens systole and finally leads to systolic standstill. The cardiac standstill from magnesium can be removed through calcium (in a half molar concentration) so that the heart again begins to beat. The excitation of ventricular autonomy through he injection of calcium and barium is possible but does not succeed with magnesium. In such experiments magnesium in general has a tonus-lessening, vagus-stimulating influence but not in the degree of potassium. In physiologic concentration a co-effect of magnesium for equilibrium in the heart is not evident, since magnesium as already stated can be omitted from the nutrient fluid without any change. On the isolated preparation of bronchial musculature a lessening of tonus is also demonstrated.
The intestinal action of magnesium salts need not be concerned with a purgative action as is known of magnesium sulphate. With MgSO4 the fluidity of the stool depends not upon a resorptive action but exactly on the poor resorption of this salt. This saline purgative substance, MgSO4 dissociates very little and has a slight capacity for diffusion: therefore the difficult absorption. The withdrawal of fluid into the intestine is according to all appearances conditioned through an increase of pure intestinal fluid. Through the difficult absorption of this salt, the fluid is held in the intestine and compels the intestine to excrete it.
Intestinal peristalsis by MgSO4 as well as by MgCl2 is depressed as well as by intravenous introduction. In the stomach of animals MgSO4 slows emptying, but increases the gastric secretion. But in man the secretion has also been found depressed.6 According to Wiechmann the magnesium paralysis of the intestine can be removed through calcium; Botazzi on the contrary discusses a synergism of magnesium and calcium.
In any case it may be assumed that magnesium and calcium have some similarity in the intestinal action even if the experimental findings are still contradictory to one another.
By MgSO4 a relaxation of the sphincter Oddi (choledochus) is produced, so that there is increased emptying of the gallbladder. The secretion of bile from the liver is rather depressed.9
The magnesium ions have an important relation to the nervous system. Injected in large doses (decigrams), the magnesium salts provoke a narcotic condition. At first a peripheral paralysis appears, and indeed like a curare effect in that the muscles loses indirect excitability. The respiratory muscles are uninvolved for some time. To this is added then a central paralysis with loss of consciousness. An increase in magnesium in the brain has not been observed quantitatively in single intoxications and only to a slight extent in repeated poisonings. After intralumbar injections motility and sensation in the lower half of the body diminish. The magnesium narcosis can be immediately interrupted through the intravenous injection of calcium, from which it may be presumed that it is concerned with an ion action. But in this antagonism of ions positively nothing is said of calcium acting stimulating on the nervous system by itself. The opposite is much more the case.